1例67岁男性原发性肝癌患者因多次介入治疗后疾病进展，改为瑞戈非尼联合信迪利单抗方案治疗，用药1个周期后出现左侧面部表情肌和左侧上睑无力，全身肌肉疼痛伴呼吸困难。实验室检查示肌红蛋白8 614 μg/L，肌酸激酶（CK）17 480 U/L，CK-MB质量528 μg/L，肌钙蛋白I 0。465 μg/L，天冬氨酸转氨酶（AST）1 069 U/L，丙氨酸转氨酶（ALT）493 U/L，乳酸脱氢酶（LDH）2 469 U/L；心电图示新发左束支阻滞。考虑为信迪利单抗所致免疫相关性肌炎、免疫相关性肌痛、免疫相关性肝炎，不除外免疫相关心脏毒性。立即停用瑞戈非尼和信迪利单抗，给予甲泼尼龙500 mg冲击治疗（5 d后逐渐减量）、甘草酸单铵半胱氨酸氯化钠注射液和双环醇保肝、降肝酶治疗。7 d后，患者左侧面部表情肌及左侧眼睑无力较前缓解，胸闷较前缓解，全身肌肉无明显疼痛；15 d后实验室检查示肌红蛋白494 μg/L，CK 537 U/L，CK-MB质量115 μg/L，LDH 519 U/L，AST 52 U/L，ALT 77 U/L。治疗半年后停用甲泼尼龙，各项指标基本恢复正常，未再使用免疫治疗。 A 67-year-old male patient with primary liver cancer was given combination treatment with regorafenib and sintilimab because of disease progression after multiple interventional therapy。 After one cycle of medication， the patient developed weakness in the left facial expression muscle and left upper eyelid， and generalized muscle pain with dyspnea。 Laboratory tests showed myoglobin 8 614 μg/L， creatine kinase (CK) 17 480 U/L， CK-MB mass 528 μg/L， troponin I 0。465 μg/L， aspartate aminotransferase (AST) 1 069 U/L， alanine aminotransferase (ALT) 493 U/L， and lactate dehydrogenase (LDH) 2 469 U/L。 The electrocardiogram showed the new onset of left bundle branch block。 It was considered to be immune-related myositis， immune-related myalgia， and immune-related hepatitis caused by sintilimab， not excluding immune-related cardiac toxicity。 Regorafenib and sintilimab were discontinued immediately while methylprednisolone pulse therapy was initiated at a dose of 500 mg (gradually reduced after 5 days)， monoammonium glycyrrhizinate and cysteine and sodium chloride injection and bicyclol were administered for liver protection and reducing liver enzyme levels。 After 7 days of treatments， weakness in the left facial expression muscle and eyelid were improved significantly along with relief from chest tightness and alleviation of generalized muscle pain throughout the body。 After 15 days of treatments， laboratory tests showed myoglobin 494 μg/L， CK 537 U/L， CK-MB mass 115 μg/L， AST 52 U/L， ALT 77 U/L， and LDH 519 U/L。 After half a year of treatments， glucocorticoids therapy was discontinued， and all indicators returned basically to normal。 The patient did not receive immunotherapy again。
Sintilimab-induced multiple organ immune-related adverse reactions
A 67-year-old male patient with primary liver cancer was given combination treatment with regorafenib and sintilimab because of disease progression after multiple interventional therapy. After one cycle of medication, the patient developed weakness in the left facial expression muscle and left upper eyelid, and generalized muscle pain with dyspnea. Laboratory tests showed myoglobin 8 614 μg/L, creatine kinase (CK) 17 480 U/L, CK-MB mass 528 μg/L, troponin I 0.465 μg/L, aspartate aminotransferase (AST) 1 069 U/L, alanine aminotransferase (ALT) 493 U/L, and lactate dehydrogenase (LDH) 2 469 U/L. The electrocardiogram showed the new onset of left bundle branch block. It was considered to be immune-related myositis, immune-related myalgia, and immune-related hepatitis caused by sintilimab, not excluding immune-related cardiac toxicity. Regorafenib and sintilimab were discontinued immediately while methylprednisolone pulse therapy was initiated at a dose of 500 mg (gradually reduced after 5 days), monoammonium glycyrrhizinate and cysteine and sodium chloride injection and bicyclol were administered for liver protection and reducing liver enzyme levels. After 7 days of treatments, weakness in the left facial expression muscle and eyelid were improved significantly along with relief from chest tightness and alleviation of generalized muscle pain throughout the body. After 15 days of treatments, laboratory tests showed myoglobin 494 μg/L, CK 537 U/L, CK-MB mass 115 μg/L, AST 52 U/L, ALT 77 U/L, and LDH 519 U/L. After half a year of treatments, glucocorticoids therapy was discontinued, and all indicators returned basically to normal. The patient did not receive immunotherapy again.
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